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Myc lacks E2F1's ability to suppress skin carcinogenesis

Oncogene volume 20, pages 5341–5349 (2001)Cite this article

Abstract

Myc and E2F1 can each stimulate proliferation, induce apoptosis, and contribute to oncogenic transformation. However, only E2F1 has been shown to have a tumor suppressive activity under some conditions. To examine the potential of Myc to suppress tumorigenesis under one of the conditions in which E2F1 functions to suppress tumorigenesis, transgenic mice expressing Myc under the control of a keratin 5 (K5) promoter were generated. Like K5 E2F1 transgenic mice, K5 Myc transgenic mice have hyperplastic and hyperproliferative epidermis and develop spontaneous tumors in the skin and oral epithelium. In addition, K5 Myc and K5 E2F1 transgenic mice both display aberrant, p53-dependent apoptosis in the epidermis. It has been demonstrated that deregulated expression of E2F1 in the epidermis of transgenic mice inhibits tumorigenesis in a two-stage skin carcinogenesis assay. In sharp contrast to those results, deregulated expression of Myc in the epidermis of transgenic mice resulted in an enhanced response to two-stage skin carcinogenesis. We conclude that while Myc and E2F1 have similar proliferative, apoptotic and oncogenic properties in mouse epidermis, Myc lacks E2F1's tumor suppressive property. This suggests that E2F1's unique ability to inhibit skin carcinogenesis is not simply a consequence of promoting p53-dependent apoptosis.

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Acknowledgements

We thank Jen Philhower and Jen Smith for expert technical assistance, Shawnda Sanders for preparation of the manuscript, Lezlee Coghlan, Dale Weiss and coworkers for animal care, and Judy Ing and Chris Yone for artwork. We also thank Andy Butler for plasmids and other reagents. This work was supported by grants from the National Institutes of Health (CA79648 to DG Johnson, CA42157 to CJ Conti, NIEHS Center Grant ES007784, and M.D. Anderson Cancer Center Grant CA16672). This work was also supported by Tobacco Settlement Funds as appropriated by the Texas State Legislature.

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  1. Science Park Research Division, University of Texas M.D. Anderson Cancer Center, Park Road 1C, Smithville, TX 78957, Texas, USA

    Robert J Rounbehler, Robin Schneider-Broussard, Claudio J Conti & David G Johnson

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  1. Robert J Rounbehler
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Correspondence to David G Johnson.

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Rounbehler, R., Schneider-Broussard, R., Conti, C. et al. Myc lacks E2F1's ability to suppress skin carcinogenesis. Oncogene 20, 5341–5349 (2001). https://doi.org/10.1038/sj.onc.1204691

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